REVIEW: A Portrait of Three Mammalian Bicistronic mRNA Transcripts, Derived from the Genes ASNSD1, SLC35A4, and MIEF1

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Dmitry E. Andreev^1,2,a*, Ivan N. Shatsky^2,b

¹Shemyakin–Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 117997 Moscow, Russia

²Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 119992 Moscow, Russia

^* To whom correspondence should be addressed.

Received: October 4, 2024; Revised: November 25, 2024; Accepted: December 7, 2024

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Recent advances in functional genomics have allowed identification of thousands of translated short open reading frames (sORFs) in the 5′ leaders of mammalian mRNA transcripts. While most sORFs are unlikely to encode functional proteins, a small number have been shown to have evolved as protein-coding genes. As a result, dozens of these sORFs have already been annotated as protein-coding ORFs. mRNAs that contain both a protein-coding sORF and an annotated coding sequence (CDS) are referred to as bicistronic transcripts. In this study, we focus on three genes – ASNSD1, SLC35A4, and MIEF1 – which give rise to bicistronic mRNAs. We discuss recent findings regarding functional investigation of the corresponding polypeptide products, as well as how their translation is regulated, and how this unusual genetic arrangement may have evolved.

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KEY WORDS: translation initiation, reinitiation, leaky scanning, dual coding, bicistronic mRNA

DOI: 10.1134/S0006297924603630

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